A Retrospective Evaluation of Risk of Peripartum Cardiac Dysfunction in Survivors of Childhood, Adolescent and Young Adult Malignancies.

Long-term survivors of childhood, adolescent and young adult (AYA) malignancies with past exposure to potentially cardiotoxic treatments are at risk of peripartum cardiac dysfunction. Incidence and risk factors for peripartum cardiac dysfunction and maternal cardiac outcomes in this population were investigated. Eligible long-term survivors were aged <30 years at cancer diagnosis, with ≥1 pregnancy occurring ≥5 years after diagnosis. "Peripartum" cardiac events were defined as occurring within pregnancy or ≤5months after delivery. Cardiac events were classified "symptomatic" or "subclinical". "Peripartum cardiomyopathy" (PPCM) was defined as symptomatic dysfunction without prior cardiac dysfunction. Of 64 eligible women, 5 (7.8%) had peripartum cardiac events: 3 symptomatic, 2 subclinical. Of 110 live births, 2 (1.8%, 95% CI 0.2-6.4) were defined as PPCM: Significantly greater than the published general population incidence of 1:3000 (p < 0.001), representing a 55-fold (95% CI 6.6-192.0) increased risk. Risk factor analyses were hypothesis-generating, revealing younger age at cancer diagnosis and higher anthracycline dose. Postpartum, cardiac function of 4 women (80%) failed to return to baseline. In conclusion, peripartum cardiac dysfunction is an uncommon but potentially serious complication in long-term survivors of paediatric and AYA malignancies previously treated with cardiotoxic therapies. Peripartum cardiac assessment is strongly recommended for at-risk patients.

The complex relationship between lung tumor volume and survival in patients with non-small cell lung cancer treated by definitive radiotherapy: a prospective, observational prognostic factor study of the Trans-Tasman Radiation Oncology Group (TROG 99.05).

BACKGROUND AND PURPOSE: To investigate the hypothesis that primary tumor volume is prognostic independent of T and N stages in patients with non-small cell lung cancer (NSCLC) treated by definitive radiotherapy. MATERIALS AND METHODS: Multicenter prospective observational study. Patient eligibility: pathologically proven stage I-III non-small cell lung cancer planned for definitive radiotherapy (minimum 50 Gy in 20 fractions) using CT-based contouring. Volumes of the primary tumor and enlarged nodes were measured according to a standardized protocol. Survival was adjusted for the effect of T and N stage. RESULTS: There were 509 eligible patients. Five-year survival rates for tumor volume grouped by quartiles were, for increasing tumor volume, 22%, 14%, 15% and 21%. Larger primary tumor volume was associated with shorter survival (HR=1.060 (per doubling); 95% CI 1.01-1.12; P=0.029). However, after adjusting for the effects of T and N stage, there was no evidence for an association (HR=1.029, 95% CI, 0.96-1.10, P=0.39). There was evidence, however, that larger primary tumor volume was associated with an increased risk of dying, independently of T and N stage, in the first 18 months but not beyond. CONCLUSIONS: In patients treated by non-surgical means we were unable to show that lung tumor volume, overall, provides additional prognostic information beyond the T and N stage (TNM, 6th edition). There is evidence, however, that larger primary tumor volume adversely affects outcome only within the first 18 months. Larger tumor size alone should not by itself exclude patients from curative (chemo)radiotherapy.

ANZCCSG BabyBrain99; intensified systemic chemotherapy, second look surgery and involved field radiation in young children with central nervous system malignancy.

BACKGROUND: ANZCCSG BabyBrain99 is a trial of intensive systemic chemotherapy with dual stem cell supported treatment, second look surgery and involved field radiation for children less than four years of age with malignant central nervous system tumours. PROCEDURE: Following primary resection, treatment included two courses of cisplatin and oral etoposide, a third course of mobilising chemotherapy (vincristine, etoposide, cyclophosphamide) with stem cell harvest, followed by intensive stem cell supported chemotherapy with high dose cyclophosphamide, etoposide and vincristine. Children were evaluated for second resection before proceeding to a second stem cell supported consolidation therapy consisting of melphalan and carboplatin. Patients then received involved field radiation therapy. RESULTS: Thirty three children with a range of diagnoses were enrolled. Nine percent of children had metastatic disease at diagnosis. Eighteen children completed treatment including irradiation. At the end of induction the event free survival was 70% (54-86). Forty eight percent of children had a complete response, 18% had stable disease and 3% had a partial response. Five year overall survival was 40% (22-56) and event free survival was 33% (17-50). Children in whom a complete resection were achieved had a significantly superior outcome compared to those children without a complete resection, 5 year EFS 60% (45-75), as compared to 22% (13-30), P-value <0.05. CONCLUSIONS: BabyBrain99 confirms that intensive stem cell supported chemotherapy can be safely administered to infants with CNS tumours however overall prognosis remains poor. Importantly, the study reinforces a complete surgical resection as an important favourable prognostic indicator. Pediatr Blood Cancer 2011;56:1055-1061. © 2011 Wiley-Liss, Inc.